T granules in human platelets function in TLR9 organization and signaling
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T granules in human platelets function in TLR9 organization and signaling. / Thon, Jonathan N; Peters, Christopher G; Machlus, Kellie R; Aslam, Rukhsana; Rowley, Jesse; Macleod, Hannah; Devine, Matthew T; Fuchs, Tobias A; Weyrich, Andrew S; Semple, John W; Flaumenhaft, Robert; Italiano, Joseph E.
in: J CELL BIOL, Jahrgang 198, Nr. 4, 20.08.2012, S. 561-74.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - T granules in human platelets function in TLR9 organization and signaling
AU - Thon, Jonathan N
AU - Peters, Christopher G
AU - Machlus, Kellie R
AU - Aslam, Rukhsana
AU - Rowley, Jesse
AU - Macleod, Hannah
AU - Devine, Matthew T
AU - Fuchs, Tobias A
AU - Weyrich, Andrew S
AU - Semple, John W
AU - Flaumenhaft, Robert
AU - Italiano, Joseph E
PY - 2012/8/20
Y1 - 2012/8/20
N2 - Human and murine platelets (PLTs) variably express toll-like receptors (TLRs), which link the innate and adaptive immune responses during infectious inflammation and atherosclerotic vascular disease. In this paper, we show that the TLR9 transcript is specifically up-regulated during pro-PLT production and is distributed to a novel electron-dense tubular system-related compartment we have named the T granule. TLR9 colocalizes with protein disulfide isomerase and is associated with either VAMP 7 or VAMP 8, which regulates its distribution in PLTs on contact activation (spreading). Preincubation of PLTs with type IV collagen specifically increased TLR9 and CD62P surface expression and augmented oligodeoxynucleotide (ODN) sequestration and PLT clumping upon addition of bacterial/viral ODNs. Collectively, this paper (a) tracks TLR9 to a new intracellular compartment in PLTs and (b) describes a novel mechanism of TLR9 organization and signaling in human PLTs.
AB - Human and murine platelets (PLTs) variably express toll-like receptors (TLRs), which link the innate and adaptive immune responses during infectious inflammation and atherosclerotic vascular disease. In this paper, we show that the TLR9 transcript is specifically up-regulated during pro-PLT production and is distributed to a novel electron-dense tubular system-related compartment we have named the T granule. TLR9 colocalizes with protein disulfide isomerase and is associated with either VAMP 7 or VAMP 8, which regulates its distribution in PLTs on contact activation (spreading). Preincubation of PLTs with type IV collagen specifically increased TLR9 and CD62P surface expression and augmented oligodeoxynucleotide (ODN) sequestration and PLT clumping upon addition of bacterial/viral ODNs. Collectively, this paper (a) tracks TLR9 to a new intracellular compartment in PLTs and (b) describes a novel mechanism of TLR9 organization and signaling in human PLTs.
KW - Animals
KW - Atherosclerosis
KW - Blood Platelets
KW - Cell Compartmentation
KW - Cytoplasmic Granules
KW - Erythroid Precursor Cells
KW - Humans
KW - Mice
KW - Platelet Activation
KW - Signal Transduction
KW - Thrombopoiesis
KW - Toll-Like Receptor 9
KW - Up-Regulation
U2 - 10.1083/jcb.201111136
DO - 10.1083/jcb.201111136
M3 - SCORING: Journal article
C2 - 22908309
VL - 198
SP - 561
EP - 574
JO - J CELL BIOL
JF - J CELL BIOL
SN - 0021-9525
IS - 4
ER -